Devices and methods for excluding the left atrial appendage

ABSTRACT

Devices and methods are described for occluding the left atrial appendage (LAA) to exclude the LAA from blood flow to prevent blood from clotting within the LAA and subsequently embolizing, particularly in patients with atrial fibrillation. A foam implant is delivered via transcatheter delivery into the LAA and anchored using an internal locking system of the implant. The locking system includes deployable anchors that can be deployed after deployment of the foam implant from the delivery catheter and expansion of the foam within the LAA. The implant location can thus be verified before deploying the anchors to secure the implant. The locking system can be reversible to allow retraction of the anchors and repositioning or retrieval of the implant.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

Any and all applications for which a foreign or domestic priority claimis identified in the Application Data Sheet as filed with the presentapplication are hereby incorporated by reference under 37 CFR 1.57. Forexample, this application is a continuation in part of U.S. applicationSer. No. 14/203,187 entitled “DEVICES AND METHODS FOR EXCLUDING THE LEFTATRIAL APPENDAGE” and filed on Mar. 10, 2014, and claims the benefit ofpriority under 35 U.S.C. §119(e) of U.S. Provisional Application No.62/240,124 entitled “DEVICES AND METHODS FOR EXCLUDING THE LEFT ATRIALAPPENDAGE” and filed on Oct. 12, 2015, the entire disclosure of each ofwhich is incorporated herein by reference for all purposes and forms apart of this specification.

BACKGROUND

Field

This development relates generally to systems, devices and methods forexcluding the left atrial appendage (LAA). In particular, systems,devices and methods for excluding the LAA using an expandable foamimplant with deployable anchors are described herein.

Description of the Related Art

Atrial fibrillation (Afib) is a condition in which the normal beating ofthe left atrium (LA) is chaotic and ineffective. The left atrialappendage (LAA) is a blind pouch off the LA. In patients with Afib bloodstagnates in the LAA facilitating clot formation. These clots (or clotfragments) have a tendency to embolize or leave the LAA and enter thesystemic circulation. A stroke occurs when a clot/clot fragmentembolizes and occludes one of the arteries perfusing the brain.Anticoagulants, e.g. Coumadin, have been shown to significantly reducethe stroke risk in Afib patients. These drugs reduce clot formation butalso increased bleeding complications including hemorrhagic strokes,subdural hematoma, and bleeding in the gastrointestinal tract.

There are about 8 million people in the US and EU with Afib. About 4.6million of these patients are at a high risk for stroke and wouldbenefit from anticoagulation. A large portion of these patients cannottake anticoagulants due to an increased bleeding risk, leaving theirstroke risk unaddressed. The prevalence of Afib increases with age.

Several devices for occluding the LAA are described in the prior art andeach has limitations this invention improves upon. The prior art devicesare metal structures which are circular in cross section and are made toexpand to fill the LAA ostium. These devices are offered in many sizesand must be closely matched to the highly variable LAA anatomy. This isdifficult to do using fluoroscopy and often requires adjunctive imagingin the form of transesophageal echocardiography (TEE), cardiac CT andMRI, all with three dimensional reconstructions. If the device issignificantly oversized, the LAA ostium may become overstretched leadingto tearing, resulting in bleeding into the pericardial space. If thedevice is too small, it will not adequately seal the ostium and may beprone to embolization. Even if sized correctly, the device forces theoval LAA ostium to take the round shape of the device, often resultingin residual leakage at the edges due to poor sealing.

Anchoring of these implants in the proper location is described in theprior art devices predominately using an array of radially disposedbarbs or hooks that engage into the surrounding cardiac tissue uponexpansion of the device. The device must therefore have sufficientspring force or stiffness for the barbs to engage the surroundingtissue. These barbs may lead to leaking of blood through the tissue intothe pericardial space which may lead to cardiac tamponade. Furthermore,the geometry of these barbs and hooks prevent repositioning once theimplant is fully expanded.

For all of these reasons it would be desirable to have a device whichconforms to the oval shape of the LAA, does not require an excessivenumber of sizes therefore negating the need for extensive pre-procedureimaging, can be easily repositioned after it is fully expanded, thensecured in place once the final position has been optimized.

SUMMARY

The embodiments disclosed herein each have several aspects no single oneof which is solely responsible for the disclosure's desirableattributes. Without limiting the scope of this disclosure, its moreprominent features will now be briefly discussed. After considering thisdiscussion, and particularly after reading the section entitled“Detailed Description,” one will understand how the features of theembodiments described herein provide advantages over existing systems,devices and methods.

The following disclosure describes non-limiting examples of someembodiments. For instance, other embodiments of the disclosed systemsand methods may or may not include the features described herein.Moreover, disclosed advantages and benefits can apply only to certainembodiments of the invention and should not be used to limit thedisclosure.

Devices and methods are described for occluding the left atrialappendage (LAA) to exclude the LAA from blood flow to prevent blood fromclotting within the LAA and subsequently embolizing, particularly inpatients with atrial fibrillation. A foam implant is delivered viatranscatheter delivery into the LAA and anchored using an internallocking system of the implant. The locking system includes deployableanchors that can be deployed after deployment of the foam implant fromthe delivery catheter and expansion of the foam within the LAA. Theimplant location can thus be verified before deploying the anchors tosecure the implant. The locking system can be reversible to allowretraction of the anchors and repositioning or retrieval of the implant.

The devices and methods allow for occluding the LAA with a foam plug toprevent blood from clotting within the LAA and subsequently embolizing.An implantable device is delivered through a catheter that is trackedover a guide wire through the vascular system. The guide wire lumenwithin the foam is expandable, to allow for placement of the guide wire,then is self-closing upon removal of the guide wire. Foams, which can betubular in shape with a central lumen, are described that are collapsedfor delivery and then expand in place within the LAA. The plug isanchored by tissue ingrowth from the left atrium (LA) and LAA into thefoam, by independent and/or integrated repositionable anchors, barbs,and/or by distal anchoring elements. For example, independentrepositionable anchors are described which deploy through openings inthe compressible foam plug and tubular film and can be expanded,re-collapsed, and locked through the central guide wire lumen.Repositionable atraumatic anchor system embodiments are also disclosedwhich can be independent structures or integral to the foam plug and/orskin. Foam plugs are described that are encapsulated with jackets orskins that can be tubular in shape that are sufficiently strong toenable handling of the plugs without tearing, allow for repositioningand retrieval of the plugs, provide a thromboresistant surface withinthe LA which will encourage formation of a neointima, assist in thecreation of occlusion zones designed to encourage thromboresistance andendothelialization from the blood and adjacent tissue and anchoringzones designed to promote fast and tenacious tissue ingrowth into thecompressible implant from the adjacent non-blood tissue, and can assistin closure at the ostium. These jackets or skins can be independent orcan be attached to the foam plugs. Retrieval finials can be attached atone or more points to aid in retrieval of an embolized device and toincrease radiopacity.

In one aspect, a left atrial appendage occlusion device is described.The device includes an open cell foam body and an internal lockingsystem. The body has a proximal end, a distal end and an outer skin. Theproximal end is configured to face a left atrium and the distal end isconfigured to face the left atrial appendage following implantation inthe left atrial appendage. The body can be compressed for deliverywithin a delivery catheter and can self-expand when removed from thedelivery catheter. The internal locking system is coupled with the bodyand comprises at least one deployable tissue anchor. The deployableanchor is configured to deploy from a constrained configuration withinthe body to a deployed configuration where a tissue engaging segment ofthe anchor extends outside the body to secure the body within the leftatrial appendage. The deployable anchor is configured to deploy to thedeployed configuration after the body expands within the left atrialappendage. The deployable anchor is retractable from the deployedconfiguration to a retracted configuration within the body.

In some embodiments, the internal locking system further comprises aplurality of the deployable anchors rotatably coupled with the body,wherein the plurality of anchors are configured to rotate to thedeployed and retracted configurations. The internal locking system maycomprise four of the deployable anchors. In some embodiments, the bodyfurther comprises a plurality of axially extending slots correspondingto the plurality of anchors, wherein each of the plurality of anchors isconfigured to deploy and retract through the corresponding axial slot.

In some embodiments, the internal locking system further comprises arestraint that restrains the anchor in the constrained configuration,and the anchor is deployed from the constrained configuration to thedeployed configuration by removing the restraint from the anchor. Therestraint may be a sheath that restrains the anchor in the constrainedconfiguration by covering the anchor, wherein the anchor is deployedfrom the constrained configuration to the deployed configuration byremoving the sheath from covering the anchor. The restraint may be alasso that restrains the anchor in the constrained configuration bysurrounding the anchor, and the anchor is deployed from the constrainedconfiguration to the deployed configuration by removing the lasso fromsurrounding the anchor.

In some embodiments, the internal locking system further comprises amoveable mount coupled with an end of the anchor, and the anchor isdeployed from the constrained configuration to the deployedconfiguration by axially moving the mount.

In some embodiments, the internal locking system further comprises aconstraint configured to move over the anchor to cause the anchor toretract. The constraint may be a ring configured to slide over theanchor to cause the anchor to retract.

In some embodiments, the skin comprises ePTFE.

In some embodiments, the device further comprises at least one tissueingrowth surface on a sidewall of the body.

In some embodiments, the device further comprises a plurality ofopenings in the skin to permit tissue ingrowth into the open cell foambody. The plurality of openings of the skin may be located in ananchoring region of the device located at least between the proximal anddistal ends of the device, and the device may further comprise anocclusion region located at the proximal end of the device andconfigured to encourage thromboresistance and endothelialization fromthe blood and adjacent tissue.

In another aspect, a left atrial appendage closure system is described.The system comprises a delivery catheter and a left atrial appendageocclusion device. The delivery catheter comprises an elongate flexibletubular body, having a proximal end and a distal end and at least onelumen extending therethrough. The left atrial appendage occlusion deviceis configured to be compressed within the delivery catheter and toself-expand upon deployment from the delivery catheter. The devicecomprises a self-expandable open cell foam body coupled with an internallocking system. The internal locking system comprises a deployableanchor configured to deploy from a constrained configuration to adeployed configuration after the body expands within the left atrialappendage and is configured to retract from the deployed configurationto a retracted position within the body.

In some embodiments, the system further comprises an axially movabledeployment control extending through a lumen of the body, for deployingthe deployable anchor. The system may further comprise an axiallymovable deployment control extending through a lumen of the body, fordeploying the foam body from the distal end of the closure system. Theinternal locking system may further comprise a restraint that restrainsthe anchor in the constrained configuration, and the anchor is activelydeployed from the constrained configuration to the deployedconfiguration by removing the restraint from the anchor using an axiallymovable deployment control extending through a lumen of the body. Theinternal locking system may further comprise a moveable mount coupledwith an end of the anchor, and the anchor is actively deployed from theconstrained configuration to the deployed configuration by axiallymoving the mount using an axially movable deployment control extendingthrough a lumen of the body.

In another aspect, a method of excluding a left atrial appendage isdescribed. The method comprises advancing a guidewire into the leftatrial appendage, advancing a distal end of a delivery catheter over theguidewire and into the left atrial appendage, and deploying a leftatrial appendage occlusion device from the distal end of the deliverycatheter. The device comprises an expandable foam body coupled with aninternal locking system having a deployable anchor, and the body expandswithin the left atrial appendage upon deploying from the distal end ofthe delivery catheter. The method further comprises actively deployingthe deployable anchor after the body expands within the left atrialappendage. The deployable anchor is configured to retract from thedeployed configuration to a retracted position within the body. In someembodiments, the method further comprises retracting the deployableanchor from the deployed configuration to the retracted position.

In another aspect, a left atrial appendage occlusion device isdescribed. The device comprises an expandable foam body and an internallocking system. The body can be compressed for delivery within adelivery catheter and can self-expand when removed from the deliverycatheter. The internal locking system is coupled with the body andcomprises a deployable anchor configured to deploy from a constrainedconfiguration within the body to a deployed configuration where theanchor extends outside the body to secure the body within the leftatrial appendage. The body is configured to expand upon removal from thedelivery catheter, and the deployable anchor is configured to deploy tothe deployed configuration after the body expands.

In another aspect, a left atrial appendage occlusion device isdescribed. The device comprises an expandable foam body and an internallocking system. The body can be compressed for delivery within adelivery catheter and can self-expand when removed from the deliverycatheter. The internal locking system is coupled with the body andcomprises a deployable anchor configured to deploy from a constrainedconfiguration within the body to a deployed configuration where theanchor extends outside the body to secure the body within the leftatrial appendage. The deployable anchor is configured to retract fromthe deployed configuration to a retracted configuration within the bodysuch that the body can be repositioned within the left atrial appendage.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of the present disclosure will becomemore fully apparent from the following description and appended claims,taken in conjunction with the accompanying drawings. Understanding thatthese drawings depict only several embodiments in accordance with thedisclosure and are not to be considered limiting of its scope, thedisclosure will be described with additional specificity and detailthrough use of the accompanying drawings. In the following detaileddescription, reference is made to the accompanying drawings, which forma part hereof. In the drawings, similar symbols typically identifysimilar components, unless context dictates otherwise. The illustrativeembodiments described in the detailed description, drawings, and claimsare not meant to be limiting. Other embodiments may be utilized, andother changes may be made, without departing from the spirit or scope ofthe subject matter presented here. It will be readily understood thatthe aspects of the present disclosure, as generally described herein,and illustrated in the drawing, can be arranged, substituted, combined,and designed in a wide variety of different configurations, all of whichare explicitly contemplated and make part of this disclosure.

FIG. 1 shows the anatomy of the left atrium and left atrial appendage.

FIG. 2 shows a left atrial appendage with one foam plug embodiment inplace that uses adhesive.

FIG. 3 shows an x-ray image of a foam plug.

FIG. 4 shows a left atrial appendage with foam embodiment and distalanchor in place.

FIG. 5 shows a screw anchor.

FIG. 6 shows a longitudinal cross section of a foam plug embodiment.

FIG. 7 shows an LAA cross section.

FIG. 8 is a schematic illustration of a guide catheter approaching theostium to the left atrial appendage.

FIG. 9 is an illustration as in FIG. 8, with a guidewire placed withinthe left atrial appendage.

FIG. 10 is an illustration as in FIG. 9, with an inflatable balloon atthe distal region of the guidewire positioned within the left atrialappendage.

FIG. 11 is an illustration as in FIG. 10, with the guide catheteradvanced distally along the guidewire and into the left atrialappendage.

FIG. 12 is an illustration as in FIG. 11, showing the occlusion deviceand pusher positioned within the guide catheter.

FIG. 13 is an illustration as in FIG. 12, showing the occlusion devicepartially deployed exiting the guide catheter.

FIG. 14 is an illustration as in FIG. 13, with the occlusion devicefully deployed within the left atrial appendage.

FIG. 15 is an illustration as in FIG. 14, showing the deployment ofadhesives or other anchoring structures to retain the occlusion devicewithin the left atrial appendage.

FIG. 16 shows a plug occlusive device in longitudinal cross sectionusing metal and foam.

FIG. 17 shows a plug using metal coils and foam.

FIG. 18 shows a plug using a single metal coil.

FIG. 19 shows a plug with a dilating distal tip.

FIG. 20 shows a plug with proximal and distal caps.

FIG. 21 shows a plug adhesive delivery system.

FIG. 22 shows the delivery of an expanding foam system.

FIG. 23 shows a plug with barbs.

FIG. 24 shows a plug with a retrieval suture attachment.

FIGS. 25A and 25B show a distal anchoring system.

FIG. 26 shows an alternative distal anchoring system.

FIGS. 27A-27G are various views of an embodiment of a device forocclusion of the left atrial appendage (LAA) with an internal lockingsystem for securing the device.

FIGS. 28A-28D are various views of an embodiment of an internal lockingsystem that may be used with the various devices and plugs describedherein for occlusion of the LAA, such as the device of FIGS. 27A-27G.

FIGS. 29A-29B are sequential side views of an unlocking mechanism thatmay be used with the various devices and plugs described herein forocclusion of the LAA, such as the device of FIGS. 27A-27G.

FIG. 30 is a side view of an embodiment of a device for occlusion of theLAA having flexible anchors.

FIG. 31 is a side view of an embodiment of a device for occlusion of theLAA having flexible anchors, with stiffening tubular members in apre-deployed configuration.

FIG. 32 is a side view of the device of FIG. 31, with the stiffeningtubular members in a deployed configuration.

FIG. 33 is a side view of an embodiment of a device for occlusion of theLAA having discrete attachments of an outer skin to an internal foam.

FIG. 34 is a side view of an embodiment of a device for occlusion of theLAA including an outer rim.

FIG. 35 is a side view of an embodiment of a device for occlusion of theLAA having anchors with V-tips shown in the deployed configuration.

FIG. 36 is a side view of another embodiment of a device for occlusionof the LAA having anchors with V-tips shown in the deployedconfiguration.

FIGS. 37A-37C are side views of various embodiments of V-tips that maybe used with the anchors described herein.

FIG. 38 is a side view of an embodiment of a device for occlusion of theLAA implanted inside an LAA.

FIGS. 39A-39B are perspective views of an embodiment of a deployableanchor activated by a pull wire and shown, respectively, in theconstrained and deployed configuration, that may be used with thevarious devices for occlusion of the LAA described herein.

FIGS. 40A-40B are perspective views of an embodiment of a deployableanchor activated by a lock wire and shown, respectively, in theconstrained and deployed configuration, that may be used with thevarious devices for occlusion of the LAA described herein.

FIGS. 41A-41B are perspective views of an embodiment of a deployableanchor activated by a sheath and shown, respectively, in the constrainedand deployed configuration, that may be used with the various devicesfor occlusion of the LAA described herein.

FIGS. 42A-42D are various views of embodiments of devices for occlusionof the LAA having external deployable anchors which can be collapsed andexpanded by retraction into or out of a sheath or outer catheter.

FIGS. 43A-43C are sequential side views of an embodiment of a device forocclusion of the LAA shown, respectively, constrained by a lasso,deployed, and adjusted with a mount.

FIGS. 44A-44C are side views of an embodiment of a device for occlusionof the LAA having an adjustable two stage anchor system activated bymoving a mounting base along a rod.

While the above-identified drawings set forth presently disclosedembodiments, other embodiments are also contemplated, as noted in thediscussion. This disclosure presents illustrative embodiments by way ofrepresentation and not limitation. Numerous other modifications andembodiments can be devised by those skilled in the art which fall withinthe scope and spirit of the principles of the presently disclosedembodiments.

DETAILED DESCRIPTION

The following detailed description is directed to certain specificembodiments of the development. In this description, reference is madeto the drawings wherein like parts or steps may be designated with likenumerals throughout for clarity. Reference in this specification to “oneembodiment,” “an embodiment,” or “in some embodiments” means that aparticular feature, structure, or characteristic described in connectionwith the embodiment is included in at least one embodiment of theinvention. The appearances of the phrases “one embodiment,” “anembodiment,” or “in some embodiments” in various places in thespecification are not necessarily all referring to the same embodiment,nor are separate or alternative embodiments necessarily mutuallyexclusive of other embodiments. Moreover, various features are describedwhich may be exhibited by some embodiments and not by others. Similarly,various requirements are described which may be requirements for someembodiments but may not be requirements for other embodiments. Referencewill now be made in detail to embodiments of the invention, examples ofwhich are illustrated in the accompanying drawings. Wherever possible,the same reference numbers will be used throughout the drawings to referto the same or like parts.

The devices and related methods are described herein in connection withuse in occluding, i.e. excluding, a left atrial appendage (LAA). Thevarious figures show various embodiments of LAA occlusion devices,systems and methods for delivery of the LAA occlusion devices, and/ormethods of using the device to occlude a LAA. The various systems,devices and methods described herein may include the same featuresand/or functionalities as other LAA occlusion systems, devices andmethods as described, for example, in U.S. application Ser. No.14/203,187 entitled “DEVICES AND METHODS FOR EXCLUDING THE LEFT ATRIALAPPENDAGE” and filed on Mar. 10, 2014, and/or as described in U.S.Provisional Application No. 62/240,124 entitled “DEVICES AND METHODS FOREXCLUDING THE LEFT ATRIAL APPENDAGE” and filed on Oct. 12, 2015, theentire disclosure of each of which is incorporated herein by referencefor all purposes and forms a part of this specification.

The heart 100 is shown in FIG. 1 with the left atrial appendage (LAA)102 which is a cavity emanating from the left atrium (LA) 104. The LAA102 is quite variable in shape in all dimensions. If the heart is notbeating normally, a condition called atrial fibrillation, blood withinthe LAA becomes stagnant which promotes clot formation. If blood clotswithin the LAA, the clots may pass from the LAA 102 to the LA 104, tothe left ventricle 106 and out of the heart 100 into the aorta. Vesselsthat bring blood to the brain branch off the aorta. If the clot passesto the brain via these vessels, it may get stuck and occlude a smallvessel in the brain which then causes an ischemic stroke. Strokes havesevere morbidities associated with them.

The opening of the LAA 102 to the LA 104 is called an ostium 110. Theobject of this invention is to occlude the ostium 110 thereby sealingoff the LA 104 from the LAA 102. The ostium 110, is oval, highlyvariable and dependent of loading conditions, i.e., left atrialpressure.

One embodiment of the LAA occlusion device is shown in FIG. 2. Theocclusion device or plug 204 is placed within the LAA 200 at its openingto the LA 202. It is understood that the “plugs” described herein, suchas the plug 204, may have the same or similar features as otherimplantable “devices” described herein, such as the device 10, and viceversa. The plug 204 comprises an expandable media such as an open cellfoam which enables collapse and expansion of the plug and also toenhance ingrowth of tissue into the foam. The foam plug 204 is at leastpartially encapsulated within a thin strong layer 206 such as ePTFE(expanded polytetrafluoroethylene), polyolefin or polyester. The layer206 may be referred to herein as a “skin.” Alternatively bioabsorbablematerials could be utilized such as PLA, PGA, PCL, PHA, or collagen.This thin encapsulating layer can be oriented or otherwise modified tobe elastomeric in at least one direction, such as radially.

The plug may be made of polyurethane, polyolefin, PVA, collagen foams orblends thereof. One suitable material is a polycarbonate-polyurethaneurea foam with a pore size of 100-250 um and 90-95% void content. Thefoam could be non-degradable or use a degradable material such as PLA,PGA, PCL, PHA, and/or collagen. If degradable, the tissue from the LAAwill grow into the foam plug and replace the foam over time. The plug204 may be cylindrical in shape in an unconstrained expansion but mayalso be conical with its distal end smaller than the proximal end orreversed. It could also be oval in cross section to better match theopening of the LAA.

The foam plug 204 is oversized radially in an unconstrained expansion tofit snuggly into the LAA and may be 5-50 mm in diameter depending on thediameter of the target LAA. The length “L” of the plug is similar to orgreater than its diameter “D” such that the L/D ratio is about orgreater than about 1.0 or greater than about 1.5 or greater than about2.0 to maximize its stability. In some embodiments, the length may beless than the diameter such that the L/D ratio is less than 1.0. Thecompliance of the material is designed such that it pushes on the wallsof the LAA with sufficient force to maintain the plug in place butwithout overly stretching the LAA wall. The foam and/or skin alsoconforms to the irregular surfaces of the LAA as it expands, to providea complementary surface structure to the native LAA wall to furtherenhance anchoring and promote sealing. Thus, while some left atrialappendage occlusion devices in the prior art include a mechanical framewhich forces at least some aspect of the left atrial appendage into acircular configuration, the expandable foam implant of the presentinvention conforms to the native configuration of the left atrialappendage. In one embodiment, the structure of the foam may befabricated such that squeezing axially on the opposing ends of the foamcauses the foam to increase in diameter.

The ePTFE or foam material may be provided with one or two or moreradiopaque markers such as radiopaque threads 210 or be filled with orimpregnated with a radiopaque filler such as barium sulfate, bismuthsubcarbonate, or tungsten which permit the operator to see under x-raythe plug for proper positioning in the anatomy. An x-ray image is shownin FIG. 3 where one cannot see the foam plug 300 but can clearly see thethreads 302 and the crimp 304 (discussed below). This thread or ribbonmay be made from a radiopaque metallic wire such as platinum or tungstenor a polymer with a radiopaque filler such as barium, bismuth, tantalum,tungsten, titanium or platinum.

The outer ePTFE layer may be formed from a tube with a diameter aboutthe same diameter of the foam plug and a wall thickness between about0.0001″ and about 0.001″ thick and serves to allow one to collapse andpull on the plug without tearing the foam material. The ePTFE materialalso serves as the blood contacting surface facing the left atrium 206and has pores or nodes such that blood components coagulate on thesurface and an intimal or neointimal covering of tissue grows across itand anchors tightly to the material. Pore sizes within the range of fromabout 4μ to about 110μ, ideally 5-35μ are useful for formation andadherence of a neointima.

The outer covering 206 may be constructed of materials other than ePTFEsuch as woven fabrics, meshes or perforated films made of FEP,polypropylene, polyethylene, polyester or nylon. The covering shouldhave a low compliance (non-elastic), at least longitudinally, besufficiently strong as to permit removal of the plug, a low coefficientof friction, and be thromboresistant. The outer covering serves as amatrix to permit plug removal as most foams are not sufficiently strongto resist tearing when pulled. The plug can also be coated with orcontain materials to enhance its ultrasonic echogenic profile,thromboresistance, lubricity, and/or to facilitate echocardiographicvisualization, promote cellular ingrowth and coverage.

The outer covering has holes in it to permit contact of the LAA tissuewith the foam plug to encourage ingrowth of tissue into the foam plugpores. These holes may be 1 to 5 mm in diameter or may also be oval withtheir long axis aligned with the axis of the foam plug, the length ofwhich may be 80% of the length of the foam plug and the width may be 1-5mm. The holes may be as large as possible such that the outer coveringmaintains sufficient strength to transmit the tensile forces requiredfor removal. The holes may be preferentially placed along the device. Inone embodiment, holes are placed distally to enhance tissue ingrowthfrom the LAA wall.

In one implementation of the invention, the implant is provided withproximal and distal end caps of ePTFE, joined together by two or threeor four or more axially extending strips of ePTFE. The axially extendingstrips are spaced apart from each other circumferentially, to provide atleast two or three or four or more laterally facing windows throughwhich the open cell foam body will be in direct contact with the tissuewall of the left atrial appendage. This outer covering could be a meshor netting as well. As shown in FIG. 20, the covering 2004 is only onthe proximal and distal faces of the plug 2000. They may be glued to thefoam plug and then crimped to the center tube 2002.

The implantable plug 204 or device 10 (as described below) may beanchored and secured in place in the LAA by tissue ingrowth and/or withadditional anchoring features. In some embodiments, the plug or device10 may be anchored by tissue ingrowth alone. In some embodiments, otheranchoring means may be implemented. One means of adhering the foam plugin place within the LAA is to use an adhesive, such as a low viscositycyanoacrylate (1-200 cps). The adhesive is injected into place along thesidewall near the distal end of the foam plug 208. Holes in the ePTFEcovering permit the adhesive to interact between the foam plug 204 andthe LAA wall 200. Injection of the adhesive may be accomplished withseveral means, one of which is to inject through the catheter into thecenter lumen 212. Passages 214 serve to guide the adhesive to thecorrect location. The distal end of the foam plug must be restricted atthat time to prevent the adhesive from exiting the distal crimp 216.Alternatively, FIG. 21 shows tubes 2104 that are pre-placed through theguide catheter 2102, through the center lumen of the plug 2106 and bendbackwards in the LAA to the distal end of the plug 2100. These tubes2104 pass all the way to the proximal end of the guide catheter 2102where a fitting is attached to permit injection of the adhesive whichthen exits the small tubes 2104 at the desired location of the plug.These tubes are made of polyethylene, polypropylene or FEP so that theadhesive will not adhere to the tubes. The tubes 2104 are withdrawnafter injection through the guide catheter out of the patient.

Other one part adhesives including aqueous cross linking adhesives,polyurethane, PEG, PGA, PLA, polycaprolactone or a lycine-derivedurethane may be used. In addition, these adhesives may be made in twocomponents such that one component is adherent to the foam and thesecond injected in vivo. Also, these two component adhesives may beinjected simultaneously to mix in vivo to prevent fouling of injectiontubes.

An alternative anchoring means for plug 400 is one or two or more distalanchors as shown in FIG. 4. Wire 404 is passed through the center lumen410 into the LAA and attached to the distal wall of the LAA. In thiscase, a screw wire 408 is threaded into the wall of the LAA 406. Acloser detail of this is seen in FIG. 5 as screw 502 is shown embeddedinto the LAA wall 504 but not all the way through the epicardial surface506.

Additional means of anchoring include the use of a plurality of hooks orbarbs or graspers to grab the distal wall and baskets, malecots, distalfoam plugs and Nitinol wire birds nests that open within the LAA andpush outward on the wall or engage the protrusions of the LAA. It may bedesirable to place the plug then engage the anchor as a secondary step.One such embodiment could include a multitude of nitinol wires with aball or catch welded proximal to the anchor tip. These could be gatheredwith the delivery catheter then released when the ideal plug positionhas been confirmed.

A cross section of one embodiment is shown in FIG. 6 with foam plug 600and the left atrium face 602 and the LAA face 610. The ePTFE material604 encapsulates the foam plug 600 and its open ends are connected withan attachment structure such as a wire, suture or tubular crimp 606 overan inner tube 608. The inner tube 608 may be made of an implant gradestainless steel such as 304 or 316 grades or a cobalt-chromium alloysuch as MP35n and the crimp 606 may be made of annealed 304 or 316stainless steel or a cobalt-chromium alloy such as MP35n. This crimpalso serves as an element which can be snared should the device need tobe removed.

Referring to FIG. 6, the tubular ePTFE layer 604 extends along an innerlayer 612 which lines the guidewire lumen, and everts out around theleft atrial face 602 to form outer layer 614. A first end 616 of innerlayer 612 is disposed concentrically within a second end 618 of outerlayer 614. The first end 616 and second end 618 are clamped betweeninner tube 608 and outer crimp 606. In this manner, the implant can beencapsulated in a manner that presents a seamless left atrial face 602,and preserves the integrity of the guidewire lumen with inner tube 608.

Placement of the device is shown in FIG. 7 through 15. To close the leftatrial appendage, the left atrium (LA) must first be accessed from thevenous system. One approach is to use a Brockenbrough-style needle topuncture the atrial septum to access the LA from the right atrium (RA).The basic needle-puncture technique is performed obtaining venous accesstypically via the right femoral vein. A Mullins sheath and dilator arethen tracked over a 0.025″ or 0.032″ guide wire previously placed in thesuperior vena cava (SVC). Fluoroscopic and echocardiographic imaging,such as transesophageal echo (TEE) or intracardiac echo (ICE), aretypically utilized. If echo is not utilized, it is common to also placea pigtail catheter in the aortic root to define the location of theaortic valve, a step not necessary when using echo.

Once the Mullins sheath and dilator are in the SVC, the guide wire isremoved and a trans-septal needle is placed through the dilator. Theneedle contains a stylette to prevent skiving off of polymeric materialfrom the dilator lumen as it traverses to the tip. Once the needle isnear the dilator tip, the stylette is removed and the needle isconnected to a manifold and flushed. The Mullins sheath/dilator set andthe needle (positioned within the dilator tip) are retracted into theSVC toward the RA as a unit. As the system is withdrawn down the wall ofthe SVC into the RA and positioned in the fossa ovale, the preferredpuncture location.

Once proper position in the fossa ovale is observed, the needle isadvanced across the fossa ovale into the LA. Successful trans-septalpuncture can be confirmed by echo, pressure measurement, O₂ saturationand contrast injection. Once the needle position is confirmed to bepositioned in the LA, the sheath and dilator can be advanced over itinto the LA. In some cases, the user will first pass a guide wirethrough the needle into the LA and into an upper pulmonary vein(typically the left) prior to crossing. Alternative options include theuse of radiofrequency trans-septal needles, which are useful forcrossing very thick or hypertrophic septa, or the use of a safety wireplaced through the needle and utilized for the initial puncture.

Referring to FIGS. 8 through 15, a guide catheter 802 is placed throughthe femoral vein into the right atrium of the heart and across theintra-atrial septum into the left atrium as described above andpositioned near the LAA ostium 804. A guidewire 902 usually of 0.035″diameter is placed through guide catheter 900 and into the LAA 904. Thisguidewire 1002 may have attached to its distal end a balloon 1006 whichis inflated in the LAA and serves as a bumper to prevent guide catheter1100 from perforating the wall of the LAA. The guide catheter 1100 isthen advanced over the guide wire 1108 into the LAA 1104. A radiopaquemarker 1102 is used to guide catheter placement under fluoroscopy. Thefoam plug 1204 is then pushed through the guide catheter 1200 withpusher 1202 and is shown exiting the guide catheter 1300 slowly in FIG.13 until it is fully deployed as shown in FIG. 14. The foam plug 1404position may then be adjusted in place using the distal balloon 1408 andthe guide catheter 1400, sliding the foam plug proximally by pulling onthe balloon 1408 through shaft 1412 or sliding it distally by pushingguide catheter 1400 distally. The guide wire may also contain a pressuresensor within it such that sealing of the LAA is monitored andconfirmation of a sufficient seal is made. Once the user is happy withthe placement, the adhesive 1514 may be injected and/or mechanicalanchors be deployed anchoring the plug to the wall. The guide wireballoon 1508 is deflated, after which the guide wire is removed. In analternative embodiment, a binary adhesive system can be used where onecomponent of the binary system is bonded to the outer surface of theskin covering the foam plug. The second component can be injected at theinterface between foam plug and the wall of the LAA such that bondinghappens only at the interface minimizing the risk of adhesiveembolization.

An alternative to pushing the plug through the entire length of theguide catheter is that the plug 1204 may be initially located at thedistal end of the guide catheter 1200 as shown in FIG. 12. The guidewire1210 passes through the center of the plug 1204 and in this mode, thepusher 1202 only needs to push the plug a short ways to deploy it intothe LAA.

For alternative anchors, they may be deployed, the shafts disconnectedand removed. Disconnection mechanisms may be any of several types, suchas threaded, electrolytic detachment, or others known in the art. Insome embodiments, a suture attachment may be implemented, for example asdescribed with respect to FIG. 24.

Alternative plug concepts include a combination of foam and metalimplant as shown in FIG. 16. The foam 1600 is designed to provideingrowth of tissue and also to provide a cushion of the metal stent 1602onto the tissue of the LAA. The proximal face 1604′ of the plug iscovered in ePTFE, polyester or another thromboresistant tissue scaffoldmaterial to facilitate sealing with the desired pore size to encourageovergrowth. Stent 1602 could be made of Nitinol to enable it to packinto a 10, 12, 14, 16, 18 or 20F delivery catheter and expand to itsdesired diameter. It could be braided, laser cut or wire formed. Any ofa variety of stent wall patterns may be utilized, depending upon thedesired performance. The stent may be a balloon expandable stent, orself-expandable stent as are understood in the art. In the illustratedembodiment, a self-expandable stent 1602 comprises a plurality ofproximal apexes 1608 and distal apexes 1610 connected by a plurality ofzig zag struts 1612. A hole 1606 allows passage of the guidewire fordelivery. This design may be advantageous in that the expansion forceexerted by the plug on the LAA can be controlled separately from thefoam characteristics. Also, it may be easier to pack this concept into asmaller geometry. For example, the plug can be packed into a smallergeometry by reducing the amount of foam that must be compressed into thedelivery catheter while maintaining sufficient dilation force.

Alternatively, the foam plug may be constructed of 2 foams. One densercore to provide force, for example radial force, and an outer softerfoam to engage the tissue irregularities. The softer foam could also belocated on the proximal and/or distal ends to facilitate retrieval.

Another means of adding stiffness to the foam plug is shown in FIG. 17where a cavity 1704 in the foam plug 1700 is made and a coil of wire1702 may be advanced from the guide catheter at the proximal end 1706into the cavity 1704. As the wire enters the cavity, it expands to itspredetermined size and exerts force on the foam radially outwards. Thetype and amount of wire may be determined in vivo using x-ray guidanceto examine the radial expansion of the foam into the LAA.

Instead of wires as shown in FIG. 17, a balloon may be passed into thefoam and inflated to provide radial force while the outer foam serves toengage the tissue irregularities and tissue ingrowth. Followinginflation, the balloon may be detached from a deployment catheter andthe deployment catheter withdrawn. The balloon is preferably providedwith a valve, to prevent the escape of inflation media. Inflation mediamay be any of a variety of media which is convertible between a first,flowable state and a second, hardened state such as by cross linking orpolymerization in situ.

Another LAA plug is shown in FIG. 18 as a spring like implant wire 1800that is covered with foam 1802 to encourage ingrowth. The proximal faceof the implant is covered with a sheet of ePTFE or other tissuescaffolding material. This implant may be stretched out for delivery andreleased in place.

Rather than using a foam, a low porosity outer bag without perforationscould be placed in the LAA and then filled with a substance to providethe radial expansion. This substance may be a hydrogel, cellulose orpolyvinylacetate.

Rather than requiring the use of a separate dilation device to cross theseptum, the distal crimp element 1902 may be formed in a tapered mannersuch that it extends from the distal end of the catheter 1200 and servesas a dilating tip to dilate the opening in the septum as the catheter isadvanced. See FIG. 19.

An alternative plug design uses a foam such as cellulose sponge materialthat is compacted and dehydrated such that it can be packed into theguide catheter. This foam material 2202 may be packed into the guidecatheter as shown in FIG. 22. The foam plug 2202 is then advanced fromthe distal end of the guide catheter 2204 with a plunger 2206 into theLAA. The plug exits the guide catheter and opens to a disc shape 2210.As the foam absorbs fluid in the blood, its length expands to form acylinder 2220 filling the LAA. Expansion ratios for compressed cellulosematerials may be as high as 17:1, expanded to compressed length.

It may be advantageous to use small barbs 2302 in FIG. 23 to furtherengage the plug 2204 into the LAA. Barbs may be unidirectional orbidirectional to resist movement in either the proximal or distaldirection. These barbs are embedded into the foam plug and may be 0.1 to1 mm in height. It may be desirable to place the plug then engage thebarbs as a secondary step. One such embodiment could include a multitudeof nitinol barb wires with a ball or catch welded proximal to the barbtip. These could be gathered with the delivery catheter within a sleeveor suture then released when the ideal plug position has been confirmed.

One means of removing a device that is not functioning properly is toreleasably attach a retrieval suture 2400 to the implant, such as to theproximal cap 2402 which also passes proximally throughout the entirelength of the guide catheter 2404 in FIG. 24. If the device is to beremoved, pulling on both ends of the suture 2400 will pull the outercovering into the guide catheter 2404 which can then be removed from thepatient. If the device is properly placed, the suture 2400 may be cutand removed leaving the plug in place.

Deployment of the occlusion device has been discussed primarily in thecontext of a transvascular access. However, implants of the presentinvention may alternatively be deployed via direct surgical access, orvarious minimally invasive access pathways (e.g. jugular vein). Forexample, the area overlying the xiphoid and adjacent costal cartilagemay be prepared and draped using standard techniques. A local anestheticmay be administered and skin incision may be made, typically about 2 cmin length. The percutaneous penetration passes beneath the costalcartilage, and a sheath may be introduced into the pericardial space.The pericardial space may be irrigated with saline, preferably with asaline-lidocaine solution to provide additional anesthesia and reducethe risk of irritating the heart. The occlusion device may thereafter beintroduced through the sheath, and through an access pathway createdthrough the wall of the LAA. Closure of the wall and access pathway maythereafter be accomplished using techniques understood in the art.

Depending upon the desired clinical performance, any of the LAAocclusion devices of the present invention may be provided with a drugor other bioactive agent, which may be injected via the deploymentcatheter, or impregnated within the open cell foam or coated on theimplant. The bioactive agent may be eluted or otherwise released fromthe implant into the adjacent tissue over a delivery time periodappropriate for the particular agent as is understood in the art. Usefulbioactive agents can include those that modulate thrombosis, those thatencourage cellular ingrowth, throughgrowth, and endothelialization, andpotentially those that resist infection. For example, agents that maypromote endothelial, smooth muscle, fibroblast, and/or other cellulargrowth into the implant including collagen (Type I or II), heparin, acombination of collagen and heparin, extracellular matrix (ECM),fibronectin, laminin, vitronectin, peptides or other biologicalmolecules that serve as chemoattractants, molecules MCP-1, VECF, FGF-2and TGF-beta, recombinant human growth factors, and/or plasma treatmentwith various gases.

Anti-thrombotics can typically be separated into anti-coagulants andantiplatelet agents. Anti-Coagulants include inhibitors of factor(s)within the coagulation cascade an include heparin, heparin fragments andfractions as well as inhibitors of thrombin including hirudin, hirudinderivatives, dabigatran, argatroban and bivalrudin and Factor Xinhibitors such as low molecular weight heparin, rivaroxaban, apixaban.

Antiplatelet agents include GP 2b/3a inhibitors such as epifibitide, andabciximab, ADP Receptor agonists (P2/Y12) including thienopyridines suchas ticlopidine, clopidogrel, prasugrel and tacagrelor and aspirin. Otheragents include lytic agents, including urokinase and streptokinase,their homologs, analogs, fragments, derivatives and pharmaceutical saltsthereof and prostaglandin inhibitors.

Antibiotic agents can include, but are not limited to penicillins,cephalosportins, vancomycins, aminoglycosides, quinolonges, polymyxins,erythromycins, tetracyclines, chloraphenicols, clindamycins,lincomycins, sulfonamides, their homologs, analogs, derivatives,pharmaceutical salts and combinations thereof.

Biologic agents as outlined above maybe be added to the implant 204 andmay be injected through the delivery catheter into the space between theproximal cap 206 and the foam plug 204. This may serve as a reservoir tominimize thrombus formation during the initial implantation and reducethe need for systemic anticoagulation following device implantation.

An electronic pressure sensor may be embedded into the proximal end ofthe foam plug which may be used to transmit LA pressure to a remotereceiver outside the body for the monitoring of LA pressure which isuseful to monitor cardiac function. In addition, a cardiac pacer ordefibrillator may be embedded into the foam plug and attachedelectrically to the distal anchor. A drug delivery reservoir may beembedded with connection to the LA for controlled delivery of biologicagents as outlined above.

Another means of anchoring is shown in FIG. 25A where the foam plug 2500is placed in the LAA. The distal screw lead 2502 is advanced and screwedinto the LAA wall. Guide 2506 is pulled proximally as shown in FIG. 25B.When this guide 2506 is pulled back, the screw lead wire, made ofNitinol, bunches up into a “birds nest” 2508 or forms a coil inside thefoam plug 2500. The screw lead wire 2502 is pushed distally from theguide catheter 2504 with a pusher 2510 and continues to bunch up intothe foam. The catheter system 2504, 2506 and 2510 are then removed.

Another means of anchoring the distal anchor element to the foam isshown in FIG. 26. Two barbed leads 2604 are attached to anchor 2602 suchthat when advanced into place in the foam plug 2600, the barbs 2604 diginto the foam plug.

FIGS. 27A-27G are various views of an embodiment of a device 10 forocclusion of the left atrial appendage (LAA). The device 10 may includethe same or similar features as other devices for occlusion of the LAAdescribed herein, such as the plug 204, and vice versa. The device 10includes an internal locking system 101 for securing the device 10within the LAA. In some embodiments, the device 10 may not include theinternal locking system 101 or other anchoring features, for example thedevice 10 may be anchored by tissue ingrowth alone. The occlusion device10 comprises an expandable media such as an open cell foam body 15, forexample a plug. The body 15 enables collapse and expansion of the device10 and also enhances ingrowth of tissue into the foam.

The body 15 of the device 10 shown in FIG. 27A through FIG. 27F is inits expanded configuration. The body 15 is in a compressed configurationin FIG. 27G. The device 10 includes the foam body 15, a skin 20, acentral lumen 25, a finial 30, and a dynamic internal locking system 101which anchors the device 10 within the LAA. FIG. 27A is a sidecross-section view of the device 10 showing the body 15 and the internallocking system 101 in a deployed configuration. FIG. 27B is an end viewof the proximal end of the device 10 showing the body 15 and theinternal locking system 101 in a deployed configuration. FIG. 27C is aside view of the device 10 showing the body 15 and the internal lockingsystem 101 in a deployed configuration. FIG. 27D is a side cross-sectionview of the device 10 showing the body 15 in a deployed configurationand the internal locking system 101 in a constrained configuration. FIG.27E is an end view of the distal end of the device 10 showing the body15 and the internal locking system 101 in a deployed configuration. FIG.27F is a cross-section view of the device 10 taken along the line 1F-1Fas shown in FIG. 27C. FIG. 27G shows the body 15 and internal lockingsystem 101 loaded and compressed within a delivery sheath 1. The device10 may be delivered via a delivery catheter in the configuration shownin FIG. 27G. The body 15 of the device 10 may then expand with theinternal locking system 101 still constrained, as shown in FIG. 27D. Theinternal locking system 101 may then deploy into the deployedconfiguration as shown in FIG. 27A.

FIG. 27G shows the body 15 and internal locking system 101 loaded andcompressed within an embodiment of a delivery sheath 1. In someembodiments, the delivery sheath 1 may be an outer delivery catheter.The body 15 and internal locking system 101 are loaded and compressedwithin a delivery catheter 5. The device 10 may be entirely or partiallyinside the delivery catheter 5. In some embodiments, the deliverycatheter 5 may be an inner delivery catheter. The device 10 may beloaded and compressed with the delivery catheter 5 inside of thedelivery sheath 1. Removing the delivery sheath 1, for example byretracting the delivery sheath 1 in the proximal direction, may allowthe body 15 of the device 10 to expand. The body 15 expands while theinternal locking system 101 is still constrained, for example by thedelivery catheter 5. FIG. 27D shows the body 15 in its deployed state,with the internal locking system 101 in a constrained configurationwithin the delivery catheter 5. This demonstrates the first step in thedeployment process, specifically placement of the device 10 within theLAA where the body 15 is expanded and the internal locking system 101 isconstrained and thus the anchors are not deployed. The second step ofthe deployment process is shown in FIG. 27A where the internal lockingsystem 101 has been deployed through the body 15. In some embodiments,this second step is reversible to retract the anchors, for example ifplacement of the device 10 within the LAA is unacceptable. The internallocking system 101, for example an anchoring component or system asfurther described herein, is deployed from within the body 15 to deployat least one and in some implementations at least 2 or 4 or 6 or moreanchors of the internal locking system 101 outside the body 15 to engageadjacent anatomy of the LAA.

The internal locking system 101 may be controllably deployed a period oftime after the body 15 expands. For instance, the location, orientation,etc. of the device 10 may be verified with various imaging techniquessuch as by fluoroscopy with injection of contrast media via the centrallumen before the internal locking system 101 is deployed and the anchorssecure the device 10 within the LAA. In some embodiments, even afterdeployment of the internal locking system 101 and anchors thereof, theanchors may be retracted to a position within the body 15 forrepositioning, and/or retrieval of the device 10 from, within the LAA.

FIG. 27F shows an embodiment of the device having slots 17. The slots 17are formed within the foam body 15. For instance, material of the foambody 15 may be removed to facilitate deployment of the internal lockingsystem 101, such as outward expansion of anchors to engage the tissue.

The device 10 may have any or all of the same or similar features and/orfunctionalities as the other plugs described herein, for example theplug 204, etc. For example, the device 10 is at least partiallyencapsulated within the skin 20. In some embodiments, the skin 20 maycover the proximal end of the body 15. The skin 20 may be a thin, strongouter layer. The skin 20 may be a thin, encapsulating layer. The skin 20may be fabricated from ePTFE (expanded polytetrafluoroethylene),polyolefin, polyester, other suitable materials, or combinationsthereof. In some embodiments, the skin 20 may be fabricated frombioabsorbable materials, for example polylactic acid (PLA), Polyglycolicacid (PGA), ploycaprolactone (PCL), PHA, collagen, other suitablebioabsorbable materials, or combinations thereof. The skin 20 can beoriented or otherwise modified to be elastomeric in at least onedirection, such as radially.

The body 15 may be made of polyurethane, polyolefin, PVA, collagen foamsor blends thereof. One suitable material is a polycarbonate-polyurethaneurea foam with a pore size of 100-250 um and 90-95% void content. Thebody 15 may be non-degradable or use a degradable material such as PLA,PGA, PCL, PHA, and/or collagen. If degradable, the tissue from the LAAwill grow into the foam body 15 and replace the foam over time. The body15 may be cylindrical in shape in an unconstrained expansion but mayalso be conical with its distal end smaller than the proximal end, orvice versa. The body 15 may also be oval in cross section to bettermatch the opening of the LAA.

The device 10 is oversized radially in an unconstrained expansion to fitsnuggly into the LAA. The device 10 may be 5-50 millimeters (mm) andgenerally at least about 10 mm or 15 mm in diameter in its unconstrainedconfiguration, for example depending on the diameter of the target LAA.The length “L” of the device 10 may be less than, similar to or greaterthan its diameter “D” such that the L/D ratio is less than 1.0, about orgreater than about 1.0, greater than about 1.5, or greater than about2.0. The L/D ratio may be greater than 1.0 to maximize its stability.However, in some embodiments, the L/D ratio may be less than 1.0, forexample, from about 0.2 to about 0.9, or from about 0.3 to about 0.8, orfrom about 0.4 to about 0.6. The compliance of the material of thedevice 10 is designed such that it pushes on the walls of the LAA withsufficient force to maintain the plug in place but without overlystretching the LAA wall. The foam body 15 and/or skin 20 also conformsto the irregular surfaces of the LAA as it expands, to provide acomplementary surface structure to the native LAA wall to furtherenhance anchoring and promote sealing. Thus, the expandable foam body 15conforms to the native irregular configuration of the LAA. In someembodiments, the structure of the foam body 15 may be fabricated suchthat axial compression on the opposing ends of the body 15 such as byproximal retraction of a pull wire or inner concentric tube causes thefoam to increase in diameter.

The body 15 and/or skin 20, for example the foam material and/or ePTFE,may be provided with one, two or more radiopaque markers, such asradiopaque threads 210 (see FIG. 2) or filled with or impregnated with aradiopaque filler such as barium sulfate, bismuth subcarbonate, ortungsten, which permit the operator to visualize under x-ray the device10 for proper positioning in the anatomy. Visualization of the device 10may be used to verify the position of the device 10 before deployment ofanchors to secure the device 10 in place.

The skin 20, such as an outer ePTFE layer, may have a thickness betweenabout 0.0001 inches and about 0.0030 inches. In some embodiments, thethickness of the skin 20 may be between about 0.0003 inches and about0.0020 inches. In some embodiments, the thickness of the skin 20 may bebetween about 0.0005 inches and about 0.0015 inches. The thickness ofthe skin 20 may be uniform, for example the same or approximately thesame no matter where the thickness is measured. In some embodiments, thethickness of the skin 20 may be non-uniform, for example the thicknessmay be different in different portions of the skin 20.

The skin 20, such as an outer ePTFE layer, may also serve as the bloodcontacting surface on the proximal end of the device 10 facing the leftatrium. The skin 20 may have pores or nodes such that blood componentscoagulate on the surface and an intimal or neointimal covering of tissuegrows across it and anchors tightly to the skin material. Pore sizes maybe within the range of from about 4μ to about 110μ. In some embodiments,the pore sizes are within the range of from about 30μ to about 90μ. Insome embodiments, the pore sizes are within the range of from about 30μto about 60μ. Such ranges of pore sizes are useful for formation andadherence of a neointima. In some embodiments, the skin 20, such as anouter ePTFE layer, may be formed from a tube with a diameter about thesame diameter of the foam body 15. and allows one to collapse and pullon the body 15 without tearing the foam material.

The skin 20 may be constructed of materials other than ePTFE such aswoven fabrics, meshes or perforated films made of FEP, polypropylene,polyethylene, polyester or nylon. The skin 20 may have a low compliance(e.g. non-elastic), for instance a low compliance longitudinally, may besufficiently strong as to permit removal of the plug, may have a lowcoefficient of friction, and/or may be thromboresistant. The skin 20serves as a matrix to permit plug removal as most foams are notsufficiently strong to resist tearing when pulled. The body 15 can alsobe coated with or contain materials to enhance its ultrasonic echogenicprofile, thromboresistance, lubricity, and/or to facilitateechocardiographic visualization, promote cellular ingrowth and coverage.

The skin 20 may include holes to permit contact of the LAA tissue withthe foam body 15. Exposure of the foam body 15 to the LAA or othertissue has benefits for example encouraging ingrowth of tissue into thefoam plug pores and/or increasing friction to hold the body 15 in place.These holes may be 1 to 5 mm in diameter or may also be oval with theirlong axis aligned with the axis of the foam plug, the length of whichmay be 80% of the length of the foam plug and the width may be 1-5 mm.The holes may be as large as possible such that the outer coveringmaintains sufficient strength to transmit the tensile forces requiredfor removal. The holes may be preferentially placed along the device 10.In some embodiments, the holes are placed distally to enhance tissueingrowth from the distal LAA wall.

In some embodiments, the device 10 includes an occlusion region andanchoring region. The proximal portion of the device 10 facing the leftatrium after the device is implanted in the LAA may include theocclusion region. The occlusion region may be a blood contacting surfaceon the proximal end of the device 10 that is thromboresistant whilepromoting formation of a neointima at the occlusion region. Theocclusion zone encourages thromboresistance and endothelialization fromthe blood and adjacent tissue. The anchoring zone promotes fast andtenacious tissue ingrowth into the device 10 from the adjacent non-bloodtissue. The anchoring zone may be lateral surfaces of the device 10 thatinterface with tissue adjacent and/or within the LAA. The anchoring zonecan also include the distal end of the device 10 that faces the distalwall of the LAA after implantation.

FIGS. 28A-28D are various views of an embodiment of an internal lockingsystem 101 that may be used with the device 10. In some embodiments,multiple internal locking systems 101 may be used with the device 10.FIG. 28A is a side view of the internal locking system shown in adeployed configuration. FIG. 28B is an end view of a distal end of theinternal locking system 101 in a deployed configuration. FIG. 28C is aside view of the internal locking system 201101 in a constrainedconfiguration. FIG. 28D is a side view of an embodiment of an anchor 120of the internal locking system 101.

Any of a variety of structures may be utilized as the dynamic internallocking system 101 with the device 10. In general, at least about two orfour or six or more tissue anchors 120 may be actively or passivelyadvanced from the implantable device 10 into adjacent tissue surroundingthe implantation site. Following deployment of the device 10 andexpansion of the body 15, a tissue engaging segment 121 of the tissueanchor 120 will extend beyond the skin by at least about one, and insome implementations at least about two or four 4 mm or more. The tissueengaging segment 121 is carried by a support segment 122 of the tissueanchor 120 which extends through the foam body 15, and may be attachedto a deployment control such as a pull wire, push wire, tubular supportor other control structure depending upon the desired configuration.

The locking system 101 discussed primarily herein is a passivedeployment construction. Removal of a constraint allows the tissueanchors 120 to laterally self expand to deploy into adjacent tissue.Self expansion may be accomplished by constructing the tissue anchor 120using nitinol, Elgiloy, stainless steel or other shape memory or springbias materials. The constraint may be removed by proximal retraction ordistal advance until the tissue anchors 120 are no longer engaged by theconstraint, depending upon the construction of the locking system 101.

Alternatively, tissue anchors 120 may be deployed actively such as bydistal advance, proximal retraction or rotation of a control, orinflation of a balloon positioned within the device 10 to actively drivethe anchors 120 through the skin 20 or corresponding apertures on theskin 20 and into tissue. For example, a plurality of support segment122, such as struts, may be joined at a distal end to a central hub 111,and incline radially outwardly in the proximal direction. Proximalretraction of the hub 111 will cause the tissue engaging segment 121 toadvance along its axis beyond the skin 20 and into the adjacent tissue.The inclination angle of the support segment 122, for example thestruts, may be reversed, in another construction, such that distaladvance of the hub 111 will deploy the tissue engaging segments 121beyond the skin 20. Proximal or distal advance of the hub 111 may beaccomplished by proximal or distal advance of a control such as acontrol wire or inner tube releasably engaged with the hub 111.

Depending upon the desired clinical performance, the tissue anchors 120may be retractable, such as by axial distal or proximal movement of thecontrol depending upon the inclination angle of the anchors 120. In theembodiment primarily illustrated herein, re-sheathing the anchors 120may be accomplished by advancing the tubular constraint along the rampedsurface of the tissue anchor 120 to move the anchor 120 radiallyinwardly towards the central longitudinal axis of the device 10. In thecase of an anchor 120 which deploys by advance along its ownlongitudinal axis, the anchor 120 may be retracted by advancing thecontrol in the opposite direction from the direction advanced to deploythe anchors 120.

Referring to FIGS. 28A-28D, the internal locking system 101 includes acentral tubular element or hub 111 and anchors 120. The anchors 120 maybe arms, segments, or other members extending from the hub 111. Eachanchor 120 may comprise a tissue engaging segment 121 and a supportsegment 122 which extends to the hub 111 or other control. The internallocking system 101 has a single central tubular hub 111 and a multitudeof the anchors 120. As shown, there are four anchors 120. There may betwo, three, four, five, six, seven, eight, or more anchors 120. Theanchor 120 may be rotatably, hingedly, or otherwise moveably coupledwith the hub 111. The anchor 120 may thus move relative to the hub 111,for example after being released from a restraint holding the anchor 120in a constrained configuration to deploy into a deployed configuration.As further example, the anchor 120 may move from the deployedconfiguration to a retracted position, as further described herein. Theanchor 120 may be curvilinear as shown, for example to allow the anchor120 to take the geometry shown in FIG. 28A when unconstrained.

The illustrated anchor 120 may have a distal region 130, a hinge region135, and/or a proximal region 125. The distal region 130 interacts withthe hub element 111. The hinge region 135 and the curvilinear geometryas shown allow the end of the proximal region 125 to extend beyond thebody 15, for example beyond a sidewall of the body 15. The proximalregion 125 includes a tissue engaging segment 121 configured to engageadjacent tissue. The tissue engaging segment 121 may be the entireproximal region 125 or a portion thereof, for example the tip, etc. Theproximal region 125 may thus include a sharpened tissue engaging segment121, a shaped tissue engaging segment 121, an angled tissue engagingsegment 121, a thickness configured for tissue engagement, and/or othersuitable features. In some embodiments, the proximal region 125 mayretract back within the body 15, as further described herein. In theembodiment shown, the anchor 120 and central tube 111 are distinctelements which are affixed to one another as shown. In otherembodiments, the anchor 120 and tube 111 are a single, integral unit.

The internal locking system 101 is made from biocompatible metallic wiresuch as Nitinol, implant grade stainless steel such as 304 or 316, orcobalt-chromium based alloys such as MP35N or Elgiloy. In someembodiments, the internal locking system 101 may be cut from a singletubular piece of metal fabricated via machining or laser cuttingfollowed by a secondary forming or annealing step using similarmaterials.

The internal locking system 101 may be in a constrained configuration asthe device 10 is placed in position in the LAA and the body 15 expandstherein. Then, in a secondary step, the internal locking system 101locks or otherwise secures the device 10 in the LAA by engaging theanchors 120. If the position is not considered optimal, or if the device10 otherwise needs to be repositioned within and/or removed from theLAA, the internal locking system 101 and anchors 120 thereof can beunlocked and the device 10 repositioned and/or removed.

FIGS. 29A-29B are sequential side views of an axially movable loop typeunlocking mechanism that may be used with the device 10 to release thetissue anchors. FIG. 29A is a side cross-section view of the device 10showing the tissue anchors of internal locking system 101 in a deployedconfiguration. FIG. 29B is a side cross-section view of the device 10showing the tissue anchors in a retracted configuration. An embodimentof an unlocking system 140 is shown. The unlocking system 140 includes aring 145. The ring 145 may be moved over the anchors 120 to move theanchors 120 to retracted configurations. The ring 145 may be moved by apull rod 147. The ring 145 may be releasably attached to the pull rod147. The pull rod 147 may extend through a catheter to engage the ring145. The unlocking system 140 may be utilized if, after the internallocking system 101 is deployed, it is desirable to unlock the device 10from within the LAA in order to reposition and/or remove the device 10.

In the illustrated construction, deployment of the tissue anchors bydistal advance of the restraint enables reversible deployment, so thatsubsequent proximal retraction of the restraint will retract the tissueanchors. Alternatively, proximal retraction of the restraint to releasethe tissue anchors will irreversibly release the tissue anchors.

FIG. 30 is a side view of an embodiment of the device 10 having flexibleanchors 401. The device 10 shown in FIG. 30 may have the same or similarfeatures and/or functionalities as the other devices for excluding theLAA described herein, and vice versa. The device 10 may be in theconfiguration shown in FIG. 30 adjacent to or within a left atrium (LA)201. The device 10 in FIG. 30 includes the expandable body 15, such asan open cell foam body, which enables collapse and expansion of thedevice 10, and at least partially encased within the skin 20, which maybe a thin, strong layer fabricated from ePTFE (expandedpolytetrafluoroethylene), polyolefin, or polyester which assists withhealing, anchoring, and retrieval. The device 10 may also be deployed,and, if desired, repositioned and/or retrieved, or the device 10 may bepermanently fixated within the LAA by engaging an anchoring system, suchas the internal locking system 101, as described herein. The anchors401, which may be metallic, may be fabricated from Nitinol. The anchors401 may be small diameter Nitinol wire approximately 0.001 inches toapproximately 0.010 inches in diameter. In some embodiments, the anchors401 may be approximately 0.0005 inches to approximately 0.020 inches indiameter. The anchors 401 may be deployed upon expansion of the body 15.For example, the anchors 401 may self-deploy upon deployment of thedevice 10 from a delivery catheter. The anchors 401 may be relativelyshort and extremely flexible. The anchors 401 may be unable to penetratethe tissue or cause any anchoring immediately after deployment of thedevice 10.

FIG. 31 is a side view of an embodiment of a device 10 for occlusion ofthe LAA having anchors 401 with tubes 500. The device 10 may bepositioned adjacent to or within the left atrium (LA) 201. The anchors401 may be flexible anchors, or in some embodiments the anchors 410 maybe relatively stiffer, as further described. The tubes 500 may bestationary or moveable tubes, as further described. In some embodimentsthe tubes 500 are hypotubes. The tubes 500 may be stainless steel,polyamide, or other suitable materials. The tubes 500 may surround acorresponding anchor 401, as further described.

In some embodiments, the anchors 401 may be fixed such that they do notmove axially. For example, the anchors 401 may have a portion, such as atissue engaging segment 121, of a fixed length extending outside thebody 15. The portion of the anchors 401 extending outside the body 15may be bent when compressed within a delivery catheter and/or sheath,and these portions of the anchors 401 may then straighten out to theconfiguration shown in FIGS. 31 and 32 after deployment of the body 15.The fixed length portion of the anchors 401 extending beyond the body 15may be from about 1 mm to about 5 mm, or from about 1.5 mm to about 4mm, or from about 2 mm to about 3 mm. This length of exposed anchor 401outside the body 15 may be effectively shortened by deployment of acorresponding tube 500, as further described. Deployment of thecorresponding tube 500 about the corresponding anchor 400 may shortenthe effective length of exposed anchor 401, i.e. the length of theanchor 401 extending beyond the end of the tube 500 after deployment ofthe tube 500, from about 0.5 mm to about 1 mm. These are merely examplesof different lengths of the anchor 401 and other suitable lengths may beimplemented.

In some embodiments, the anchors 401 may be moveable axially. Forexample, the anchors 401 may not deploy or otherwise extend outside thebody 15 immediately upon expansion of the body 15. Following acceptablepositioning of the device 10 within the LAA, the flexible anchors 401may then be advanced through a corresponding tube 500. The anchors 401may move axially in any suitable manner, including those describedelsewhere herein. The anchor 401 may be moved through the tube 500either before or after the tube 500 has been moved and deployed outsidethe body 15, as described below.

In some embodiments, the tubes 500 are moveable and deploy outside thebody 15. The tubes 500 may be moveable in embodiments having eitherfixed or moveable anchors 401. The tubes 500 may be pre-loaded overcorresponding wire anchors 401 as shown in FIG. 31, for example one tube500 per anchor 401. The tube 500 may then be moved over thecorresponding anchor 401 as shown in FIG. 32. The tube 500 maystraighten the anchor 401 and add mechanical integrity. The tube 500 mayalso act as a perforation protector to prevent the anchor 401 frompuncturing through the wall of the LAA. Movement of the tube 500 overthe corresponding anchor 401 may shorten the exposed length of theanchor 401, as described. This may provide for a stiffer tissue engagingsegment of the anchor 401 due to the shortened exposed length.

In some embodiments, the tubes 500 extend from the delivery catheter toor near the outer surface of the body 15 but do not extend outside thebody 15. Instead, the tubes 500 just guide the anchor 401, for examplearound the curve, and support the wire 401 right up to tissuepenetration. The tubes 500 may set the launch angle so the anchor 401does not buckle and hits the tissue at the right angle. In thisembodiment, the anchor 401 may have relatively more stiffness than inthe embodiments where the anchors 401 are relatively flexible, in orderto provide a more secure anchoring of the device 10 to the tissue. It isunderstood the tube 500 may provide this guiding function to thecorresponding anchor in any of the embodiments described herein havingmoveable anchors, such as the moveable anchors 401, the anchors 120,etc.

The flexible anchors 401 and/or the external stiffening tube 500 may bemade from biocompatible metallic materials such as Nitinol, implantgrade stainless steel such as 304V or 316LVM, cobalt-chromium basedalloys such as MP35N or Elgiloy, other suitable materials, orcombinations thereof. The anchor 401 length can vary from 0.1 mm to 5 mmin length with an external stiffening tube 500 that covers from 10% to90% of the exposed length of the anchor 401.

The skin 20 at least partially surrounds the body 15 and portions of theskin 20 may or may not be attached to the body 15. The various devices10 described herein may have the body 15 at least partially encasedwithin the skin 20, which may be fabricated from a material such asePTFE (expanded polytetrafluoroethylene), polyolefin, or polyester whichassists with healing, anchoring, and retrieval. FIG. 33 is a side viewof an embodiment of a device 10 for occlusion of the LAA having discretepoints of attachment 700 of the skin 20 to the internal foam body 15.For clarity, the points of attachment 700 are shown as dots in thefigures. It is understood the points of attachment 700 may not bevisible from outside the device 10, for example the skin 20 may bebonded to the body 15 at the points of attachment 700, etc. In someembodiments, in addition or alternatively to bonding, the skin 20 may besecured for example with sutures to the body 15 at the points ofattachment 700, and thus some or all of the points of attachment 700 maybe visible from outside the device 10. The device 10 may be in theconfiguration shown in FIG. 33 adjacent to or within the left atrium(LA) 201. The skin 20 may be attached to the body 15 at the variousseparate points of attachment 700. As shown in FIG. 33, the skin 20 canbe partially attached, with portions thereof not attached at all, to thebody 15. This may allow, for example, the skin 20 to move duringexpansion of the body 15 that occurs after deployment of the device 10from the delivery catheter. The skin 20 may, in some embodiments, beattached at points of attachment 700 located near the proximal side ofthe device 10, for example to help promote closure of the ostium of theLAA, such as with a rim 800 as described below. The skin 20 may, forexample, be tacked in place in one or more points of attachment 700 nearthe proximal face so that any bunching of the skin 20 that occurs duringimplantation occurs near the ostium but within the LAA. This can beachieved using sutures, adhesive bonding, heat bonding, other suitableapproaches, or combinations thereof.

The selective location of the points of attachment 700 may facilitatewith formation of a circumferential rim 800 of the skin 20. The rim 800is shown schematically in FIG. 34 as a triangular rim for clarity. It isunderstood the rim 800 may be a variety of different shapes depending onthe configuration of the device 10, the shape of the LAA, etc. Further,the rim 800 may extend completely or partially around the device 10. Therim 800 may surround the ostium of the LAA. The formation of the rim 800may help to completely seal the entrance to the LAA around the device 10and thereby prevent leakage. The attachment points 700 between the skin20 and the body 15 can prevent irregular bunching of the fabric andinstead guide any excess material to form the sealing rim 800 around ornear the proximal face of the device 10, as shown in FIG. 34. The rim800 may form upon expansion of the body 15 after deployment from thedelivery catheter, as described herein. Alternatively the attachmentpoints 700 can be designed so as to prevent any bunching at all of thefabric and provide a smooth surface, such as a smooth proximal surface.

FIGS. 35-36 are side views of embodiments of the device 10 havinganchors 120 with V-tips 901 shown in the deployed configuration. TheV-tips may be located in the proximal region 125 and/or may form all orpart of the tissue engaging segment 121 of the anchor 120, as describedherein. The V-tips 901 form a V-shaped point. The V-tips 901 aregenerally in the shape of a “V” or an otherwise angled, segmented shape.The V-tips 901 may be sharp barbs or hooks. The V-tips 901 may be formedfrom wire or laser-cut tubing or other suitable methods. As shown inFIG. 35, one or more of the V-tips 901 are attached to the body 15encased in the skin 20. The V-tips 901 can be attached to the body 15and/or to the skin 20. In some embodiments, the V-tips 901 are ends ofanchors 1000. For example, the V-tips 901 may be part of the anchors1000 that are within the body 15 and skin 20, as shown in FIG. 36. Thedistal ends of the V-tips 901 may be free to slide along and collapse orexpand. The distal ends of the V-tips 901 may be attached to the body15, skin 20, and/or the anchors 1000 to allow the V-tips 901 to collapseand retract. During retrieval into a catheter or sheath, the V-tips 901can flatten out when engaging the inner diameter of the catheter orsheath. The V-tips 901 can be formed from Nitinol, implant gradestainless steel such as 304 or 316, cobalt-chromium based alloys such asMP35N or Elgiloy, other suitable materials, or combinations thereof. TheV-tips 901 may then recover their pre-set shape after deployment orre-deployment.

FIGS. 37A-37C are side views of various embodiments of V-tips that maybe used with the anchors described herein. FIG. 37A is a side view of anembodiment of the V-tip 901. The V-tip 901 includes two angled segments.The segments may form the angle in a free state. The angle may bevarious angular amounts. In some embodiments, the angle formed by theV-tip 901 is no more than about 170°, 160°, 150°, 140°, 130°, 120°,110°, 100°, 90°, 80°, 70°, 60°, or any smaller, greater or intermediateangular amount. FIG. 37B is a side view of an embodiment of a wave V-tip1101. The wave V-tip 1101 may include a curved segment and an angledstraight segment. FIG. 37C is a side view of an embodiment of a two-waveV-tip 1103. The two-wave V-tip 1103 may include two curved segments. Thecurved segments may promote engagement of the tip with the inner wall ofthe LAA. The end of the various V-tips may be smooth and rounded orsharp to promote tissue penetration. In some embodiments, all of theV-tips may have the same shape. In some embodiments, some of the V-tipsmay have a first shape and other V-tips may have a second shapedifferent from the first shape. In some embodiments, some of the V-tipsmay be attached to the skin 20 and or body 15. In some embodiments, someof the V-tips may be attached to the anchors 1000.

FIG. 38 is a side view of an embodiment of a device 10 for occlusion ofthe LAA implanted inside an LAA 1201. The device 10 includes a body 15with a skin 20 and finial 30 placed within the LAA 1201. The LAAincludes a thicker proximal portion 1203 closer to the ostium. Theinternal locking system 101, for example anchors thereof, may beconfigured to engage with the thicker proximal portion 1203 of the LAA.The various anchors, V-tips etc. described herein for the variousembodiments of the device 10 may be used to secure the anchors in thethicker proximal portion 1203. In some embodiments, the device 10 may bedeployed from the catheter such that the body 15 expands. The location,orientation, etc. of the expanded body 15 within the LAA may beverified, for example by imaging, as described herein. The location,orientation, etc. of the expanded body 15 within the LAA may be verifiedto ensure engagement of the internal locking system 101, for exampleanchors thereof, with the thicker proximal portion 1203. Then, theinternal locking system 101, for example anchors thereof, may bedeployed to engage the thicker proximal portion 1203. If afterdeployment of the internal locking system 101, for example anchorsthereof, it is determined that the anchors did not engage with thethicker proximal portion 1203, the anchors may be retracted, asdescribed herein, in order to reposition and/or retrieve the device 10.

In some embodiments, the internal locking system 101, for exampleanchors thereof, may be preloaded surface elements releasablyconstrained or otherwise locked down in a collapsed or constrainedposition or configuration. The internal locking system 101, for exampleanchors thereof, may be constrained using a restraint. The restraint maybe a dissolvable polymer, a lasso, or wires that can be retracted torelease the anchors. The restraint may be similar to a deadbolt. Otheranchoring concepts include Velcro integral to the ePTFE, electricallyorientable/ratcheting anchoring elements, unidirectional Gecko tape, orwires pre-attached to the finial 30. In some embodiments, the body 15with skin 20 may be secured within the LAA by texturing the body 15 andexposing the body 15 to the tissue through holes in the skin 20 toincrease the friction with the cardiac surface to a high enough level toprevent implant migration.

FIGS. 39A-39B are perspective views of an embodiment of a deployableanchor 1302 activated by a pull wire 1301 and shown, respectively, inthe constrained and deployed configuration, that may be used with thevarious devices 10 for occlusion of the LAA described herein. Atwo-stage anchoring system allows deployment of the anchors 1302 afterimplantation and expansion of the body 15. This embodiment incorporatesone or more hinged anchors 1302. The anchors 1302, which be a barb orother anchoring element, may lie flat during delivery and duringdeployment of the body 15. Next, when pulled or pushed, the anchors 1302bend at a hinge 1306 and extend outward from the surface of the body 15and into the LAA tissue. The anchors 1302 may bend at the hinge 1306using a hollow constraining element 1304 which can be a thin, metallic,round or rectangular box such as a round or rectangular shaped tube, andthe pull wire 1301, for example a sliding element, which can be a wireor suture. The pull wire 1301 is attached to the proximal end of theanchor 1302 and extends back through the delivery catheter or sheath.When the pull wire 1301 is retracted, the anchor 1302 slides back thougha slot 1308 in the tube 1304 and bends at the preformed hinge 1306. Aportion of the anchor 1302 then extends out through the slot 1308.

FIGS. 40A-40B are perspective views of an embodiment of a deployableanchor 1405 activated by a lock wire 1401 and shown, respectively, inthe constrained and deployed configuration, that may be used with thevarious devices 10 for occlusion of the LAA described herein. The anchor1405, which be a barb or other anchoring element, may be formed fromwire or a flat sheet of Nitinol or other shape memory material and heatset to be in an expanded configuration. One or more of the anchors 1405can be placed along the skin 20 or otherwise along an external surfaceof the body 15. One or more corresponding guides 1402, such as loops,may be located along the skin 20 or the body 15. The guides 1402 may belocated on both sides of the anchor 1405, as shown. The guides 1402 on afirst side of the anchor 1405 may fix the anchors 1405 in place. Theguides 1402 on a second, opposite side of the anchor 1405 may act as aguide for the lock wire 1401, which may be a restraining wire, suture,etc. The lock wire 1401 may be used to constrain the anchors 1405 in aconstrained configuration, for example in the flat position as shown inFIG. 40A. When the lock wire 1401 is retracted, the anchors 1405 deploy,as shown in FIG. 40B. The anchors 1405 may extend perpendicular to thebody 15, or at an angle.

FIGS. 41A-41B are perspective views of an embodiment of a deployableanchor 1506 activated by a sheath 1502 and shown, respectively, in theconstrained and deployed configuration, that may be used with thevarious devices for occlusion of the LAA described herein. The anchor1506, which be a barb or other anchoring element, may be formed fromwire or a flat sheet of Nitinol or other shape memory material and heatset to be in an expanded configuration.

One or more of the anchors 1506 may be placed along the skin 20 orotherwise along an external surface of the body 15. One or morecorresponding guides 1500 and locking loops 1504 may be located alongthe skin 20 or the body 15. The guides 1500 may be located on a firstside of the anchor 1506 and the locking loops 1504 may be located on asecond, opposite side of the anchor 1506, as shown. The anchors 1506 areheld in the constrained or restrained configuration or position by asheath cover 1502. The sheath cover 1502 may be tubular or rectangularin shape. The sheath cover 1502 constrains the anchors 1506. The sheathcover 1502 may constrain the anchors 1506 in a flat position as shown inFIG. 41A. When the sheath cover 1502 is retracted, the anchors 1506deploy, as shown in FIG. 41B. The anchors 1506 may extend at an angle tothe body 15, or perpendicularly.

FIGS. 42A-42D are various views of embodiments of devices 10 forocclusion of the LAA having external deployable anchors 1601, 1604 whichcan be collapsed and expanded by retraction into or out of a sheath orouter catheter. FIG. 42A is a side view of the device 10 having anchors1601 constrained by a delivery sheath 1603. FIG. 42B is a side view ofthe device 10 unconstrained by the delivery sheath 1603 with the anchors1601 deployed. FIG. 42C is a side view of the device 10 having anchors1604 constrained by the delivery sheath 1603. FIG. 42D is a side view ofthe device 10 unconstrained by the delivery sheath 1603 with the anchors1604 deployed. The body 15 with skin 20 can contain the anchors 1601 or1604 which are fixed to the surface of the skin 20 and are unconstrainedand therefore expanded in a free state, as shown in FIGS. 42B and 42D.The delivery sheath 1603, such as a catheter, may be used to constrainthe anchors 1601 or 1604. The anchors 1601 or 1604 may then expand whenthe body 15 is unconstrained by the delivery sheath 1603, for examplewhen the when the body 15 is released from the delivery sheath 1603. Theanchors 1601 may deploy into a curved shape as shown in FIG. 42B. Theanchors 1604 may deploy into an angled shape as shown in FIG. 42D. Theanchors 1603 or 1604 after deployment may point toward either theproximal or distal side of the body 15.

FIGS. 43A-43C are sequential side views of an embodiment of a device 10for occlusion of the LAA shown, respectively, constrained by a lasso1707, deployed, and adjusted with a mount 1705. One or more anchors 1709may be pre-mounted within the body 15 and attached distally to the mount1705. The mount 1705 may be a ring-like member having an openingextending therethrough. The mount 1705 is positioned over a 1701 rod1711. The mount 1705 can move, for example slide, over the 1701 rod 1711in the proximal direction. In some embodiments, the mount 1705 may bepulled proximally, for example by a pull wire. In some embodiments, themount 1705 may move when the 1701 rod 1711 is rotated. In someembodiments, the mount 1705 and/or 1701 rod 1711 may be threaded.Movement of the mount 1705 causes the anchor 1705 to move. The devicemay include a tapered cone 1708. The cone 1708 may be attached to theend of the rod 1711. The mount 1705 may be moved toward the cone 1708 toadjust the height of the anchors 1709. Thus, the anchors 1709 are angledmore in FIG. 17C relative to FIG. 17B. The anchor 1709 may move throughthe body 15 and into the tissue. The anchors 1709 may be adjusted toincrease or decrease the amount of tissue penetration, for example bymoving the mount 1705 as described. For retrieval, this process can bereversed. In some embodiments, the lasso 1707, attached to a wire 1703,may extend, for example thread, through the threaded 1701 rod 1711 andbe placed around the anchors 1709 to retract the anchors 1709 back intothe body 15. In some embodiments, the lasso 1707 may be used toinitially constrain the anchors 1709 and then retract to allow theanchors 1709 to deploy.

FIGS. 44A-44C are side views of an embodiment of a device 10 forocclusion of the LAA having an adjustable two stage anchor system withanchors 1801 activated by moving a mount 1803 along a rod 1804. Theanchors 1801 may be internal grappling hook type structures placedwithin the body 15 and skin 20. The anchors 1801 may be introducedthrough a central lumen 1003 that extends through the body 15, as shownin FIG. 43A. The anchors 1801 may then travel through the body 15 andskin 20 to engage tissue, as shown in FIG. 43B. The anchors 1801 may beadjusted to increase or decrease the amount of tissue penetration. Theanchors 1801 are attached at distal ends to the moveable mount 1803. Themount 1803 is prevented from rotating, for example the mount 1803 may benotched to prevent rotation of the mount 1803 within the finial 30, asshown in FIG. 43C. The mount 1803 is threaded onto the threaded rod 1804that can be rotated clockwise or counter clockwise to change the linearposition of the mount 1803. The distal end of the rod 1804 may couplewith a cap 1807. The cap 1807 may rotate with the rotation of the rod1804. The mount 1803 may move proximally causing the anchors 1801 toextend past the surface of the body 15 and skin 20 as shown in FIG. 43B.The mount 1803 may move distally to pull the anchors 1801 back within orunder the surface of the skin 20. The depth of penetration of theanchors 1801 may be controlled, for example to account for thenon-circular cross-section of the LAA. In some embodiments, the anchors1801 may be deployed individually. Another option is to deploy theanchors 1801 distal to the body 15 with skin 20 and control thestiffness of the anchors 1801 such that they apply a reasonably uniformpenetrating force to the tissue at contact.

Various modifications to the implementations described in thisdisclosure will be readily apparent to those skilled in the art, and thegeneric principles defined herein can be applied to otherimplementations without departing from the spirit or scope of thisdisclosure. Thus, the disclosure is not intended to be limited to theimplementations shown herein, but is to be accorded the widest scopeconsistent with the claims, the principles and the novel featuresdisclosed herein. The word “example” is used exclusively herein to mean“serving as an example, instance, or illustration.” Any implementationdescribed herein as “example” is not necessarily to be construed aspreferred or advantageous over other implementations, unless otherwisestated.

Certain features that are described in this specification in the contextof separate implementations also can be implemented in combination in asingle implementation. Conversely, various features that are describedin the context of a single implementation also can be implemented inmultiple implementations separately or in any suitable sub-combination.Moreover, although features can be described above as acting in certaincombinations and even initially claimed as such, one or more featuresfrom a claimed combination can in some cases be excised from thecombination, and the claimed combination can be directed to asub-combination or variation of a sub-combination.

Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. Additionally, other implementations are within the scope of thefollowing claims. In some cases, the actions recited in the claims canbe performed in a different order and still achieve desirable results.

It will be understood by those within the art that, in general, termsused herein are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to embodiments containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, those skilled in the art will recognize that such recitationshould typically be interpreted to mean at least the recited number(e.g., the bare recitation of “two recitations,” without othermodifiers, typically means at least two recitations, or two or morerecitations). Furthermore, in those instances where a conventionanalogous to “at least one of A, B, and C, etc.” is used, in generalsuch a construction is intended in the sense one having skill in the artwould understand the convention (e.g., “a system having at least one ofA, B, and C” would include but not be limited to systems that have Aalone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). In those instances where aconvention analogous to “at least one of A, B, or C, etc.” is used, ingeneral such a construction is intended in the sense one having skill inthe art would understand the convention (e.g., “a system having at leastone of A, B, or C” would include but not be limited to systems that haveA alone, B alone, C alone, A and B together, A and C together, B and Ctogether, and/or A, B, and C together, etc.). It will be furtherunderstood by those within the art that virtually any disjunctive wordand/or phrase presenting two or more alternative terms, whether in thedescription, claims, or drawings, should be understood to contemplatethe possibilities of including one of the terms, either of the terms, orboth terms. For example, the phrase “A or B” will be understood toinclude the possibilities of “A” or “B” or “A and B.”

What is claimed is:
 1. A left atrial appendage occlusion device,comprising: an open cell foam body having a proximal end, a distal endand an outer skin, the proximal end configured to face a left atrium andthe distal end configured to face the left atrial appendage followingimplantation in the left atrial appendage, wherein the body can becompressed for delivery within a delivery catheter and can self-expandwhen removed from the delivery catheter; and an internal locking systemcoupled with the body and comprising at least one deployable tissueanchor, the deployable anchor configured to deploy from a constrainedconfiguration within the body to a deployed configuration where a tissueengaging segment of the anchor extends outside the body to secure thebody within the left atrial appendage, wherein the deployable anchor isconfigured to deploy to the deployed configuration after the bodyexpands within the left atrial appendage, and wherein the deployableanchor is retractable from the deployed configuration to a retractedconfiguration within the body.
 2. The left atrial appendage occlusiondevice of claim 1, the internal locking system further comprising aplurality of the deployable anchors rotatably coupled with the body,wherein the plurality of anchors are configured to rotate to thedeployed and retracted configurations.
 3. The left atrial appendageocclusion device of claim 2, wherein the internal locking systemcomprises four of the deployable anchors.
 4. The left atrial appendageocclusion device of claim 2, the body further comprising a plurality ofaxially extending slots corresponding to the plurality of anchors,wherein each of the plurality of anchors is configured to deploy andretract through the corresponding axial slot.
 5. The left atrialappendage occlusion device of claim 1, the internal locking systemfurther comprising a restraint that restrains the anchor in theconstrained configuration, wherein the anchor is deployed from theconstrained configuration to the deployed configuration by removing therestraint from the anchor.
 6. The left atrial appendage occlusion deviceof claim 5, wherein the restraint is a sheath that restrains the anchorin the constrained configuration by covering the anchor, wherein theanchor is deployed from the constrained configuration to the deployedconfiguration by removing the sheath from covering the anchor.
 7. Theleft atrial appendage occlusion device of claim 5, wherein the restraintis a lasso that restrains the anchor in the constrained configuration bysurrounding the anchor, wherein the anchor is deployed from theconstrained configuration to the deployed configuration by removing thelasso from surrounding the anchor.
 8. The left atrial appendageocclusion device of claim 1, the internal locking system furthercomprising a moveable mount coupled with an end of the anchor, whereinthe anchor is deployed from the constrained configuration to thedeployed configuration by axially moving the mount.
 9. The left atrialappendage occlusion device of claim 1, the internal locking systemfurther comprising a constraint configured to move over the anchor tocause the anchor to retract.
 10. The left atrial appendage occlusiondevice of claim 9, wherein the constraint is a ring configured to slideover the anchor to cause the anchor to retract.
 11. The left atrialappendage occlusion device of claim 1, wherein the skin comprises ePTFE.12. The left atrial appendage occlusion device of claim 1, furthercomprising at least one tissue ingrowth surface on a sidewall of thebody.
 13. The left atrial appendage occlusion device of claim 1, furthercomprising a plurality of openings in the skin to permit tissue ingrowthinto the open cell foam body.
 14. The left atrial appendage occlusiondevice of claim 13, wherein the plurality of openings of the skin arelocated in an anchoring region of the device located at least betweenthe proximal and distal ends of the device, and wherein the devicefurther comprises an occlusion region located at the proximal end of thedevice and configured to encourage thromboresistance andendothelialization from the blood and adjacent tissue.
 15. A left atrialappendage closure system, comprising: a delivery catheter comprising anelongate flexible tubular body, having a proximal end and a distal endand at least one lumen extending therethrough; and a left atrialappendage occlusion device configured to be compressed within thedelivery catheter and to self-expand upon deployment from the deliverycatheter, the device comprising a self-expandable open cell foam bodycoupled with an internal locking system, the internal locking systemcomprising a deployable anchor configured to deploy from a constrainedconfiguration to a deployed configuration after the body expands withinthe left atrial appendage and configured to retract from the deployedconfiguration to a retracted position within the body.
 16. The leftatrial appendage closure system of claim 15, further comprising anaxially movable deployment control extending through a lumen of thebody, for deploying the deployable anchor.
 17. The left atrial appendageclosure system of claim 15, further comprising an axially movabledeployment control extending through a lumen of the body, for deployingthe foam body from the distal end of the closure system.
 18. The leftatrial appendage closure system of claim 15, the internal locking systemfurther comprising a restraint that restrains the anchor in theconstrained configuration, wherein the anchor is actively deployed fromthe constrained configuration to the deployed configuration by removingthe restraint from the anchor using an axially movable deploymentcontrol extending through a lumen of the body.
 19. The left atrialappendage closure system of claim 15, the internal locking systemfurther comprising a moveable mount coupled with an end of the anchor,wherein the anchor is actively deployed from the constrainedconfiguration to the deployed configuration by axially moving the mountusing an axially movable deployment control extending through a lumen ofthe body.
 20. A method of excluding a left atrial appendage, the methodcomprising: advancing a guidewire into the left atrial appendage;advancing a distal end of a delivery catheter over the guidewire andinto the left atrial appendage; deploying a left atrial appendageocclusion device from the distal end of the delivery catheter, thedevice comprising an expandable foam body coupled with an internallocking system having a deployable anchor, wherein the body expandswithin the left atrial appendage upon deploying from the distal end ofthe delivery catheter; and actively deploying the deployable anchorafter the body expands within the left atrial appendage, wherein thedeployable anchor is configured to retract from the deployedconfiguration to a retracted position within the body.
 21. The method ofexcluding a left atrial appendage of claim 20, further comprisingretracting the deployable anchor from the deployed configuration to theretracted position.
 22. A left atrial appendage occlusion device,comprising: an expandable foam body, wherein the body can be compressedfor delivery within a delivery catheter and can self-expand when removedfrom the delivery catheter; and an internal locking system coupled withthe body and comprising a deployable anchor, the deployable anchorconfigured to deploy from a constrained configuration within the body toa deployed configuration where the anchor extends outside the body tosecure the body within the left atrial appendage, wherein the body isconfigured to expand upon removal from the delivery catheter, andwherein the deployable anchor is configured to deploy to the deployedconfiguration after the body expands.
 23. A left atrial appendageocclusion device, comprising: an expandable foam body, wherein the bodycan be compressed for delivery within a delivery catheter and canself-expand when removed from the delivery catheter; and an internallocking system coupled with the body and comprising a deployable anchor,the deployable anchor configured to deploy from a constrainedconfiguration within the body to a deployed configuration where theanchor extends outside the body to secure the body within the leftatrial appendage, wherein the deployable anchor is configured to retractfrom the deployed configuration to a retracted configuration within thebody such that the body can be repositioned within the left atrialappendage.